Author + information
- Received August 10, 2017
- Revision received January 18, 2018
- Accepted January 30, 2018
- Published online May 28, 2018.
- Matthew A. Cavender, MD, MPHa,b,∗ (, )
- Anna Norhammar, MDc,
- Kåre I. Birkeland, MDd,
- Marit Eika Jørgensen, MDe,f,
- John P. Wilding, MDg,
- Kamlesh Khunti, MDh,
- Alex Z. Fu, PhDi,
- Johan Bodegård, MDj,
- Betina T. Blak, PhDk,
- Eric Wittbrodt, PharmD, MPHl,
- Marcus Thuresson, PhDm,
- Peter Fenici, MDn,
- Niklas Hammar, PhDc,o,
- Mikhail Kosiborod, MDp,
- on behalf of the CVD-REAL Investigators and Study Group
- aUniversity of North Carolina, Chapel Hill, North Carolina
- bBaim Institute of Clinical Research, Boston, Massachusetts
- cKarolinska Institutet, Stockholm, Sweden
- dInstitute of Clinical Medicine, University of Oslo, Oslo, Norway, and Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- eSteno Diabetes Center, Copenhagen, Denmark
- fNational Institute of Public Health, University of Southern Denmark, Odense, Denmark
- gInstitute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom
- hDiabetes Research Centre, University of Leicester, Leicester, United Kingdom
- iGeorgetown University Medical Center, Washington, DC
- jAstraZeneca, Oslo, Norway
- kAstraZeneca, Luton, United Kingdom
- lAstraZeneca, Wilmington, Delaware
- mStatisticon AB, Uppsala, Sweden
- nAstraZeneca, Cambridge, United Kingdom
- oAstraZeneca, Gothenburg, Sweden
- pSaint Luke's Mid America Heart Institute, Kansas City, Missouri, and University of Missouri-Kansas City, Kansas City, Missouri
- ↵∗Address for correspondence:
Dr. Matthew A. Cavender, University of North Carolina at Chapel Hill, Burnett-Womack Building, 160 Dental Circle, CB 7075, Chapel Hill, North Carolina 27599.
Background Prior studies found patients treated with sodium-glucose co-transporter-2 inhibitors (SGLT-2i) had lower rates of death and heart failure (HF). Whether the benefits of SGLT-2i vary based upon the presence of cardiovascular disease (CVD) is unknown.
Objectives This study sought to determine the association between initiation of SGLT-2i therapy and HF or death in patients with and without CVD.
Methods The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study was a multinational, observational study in which adults with type 2 diabetes were identified. Patients prescribed an SGLT-2i or other glucose-lowering drugs (GLDs) were matched based on a propensity score for initiation of an SGLT-2i. Hazard ratios (HRs) for the risk of death, HF, and HF or death in patients with and without established CVD were estimated for each country and pooled.
Results After propensity score matching, 153,078 patients were included in each group. At baseline, 13% had established CVD. Compared with therapy using other GLDs, initiation of an SGLT-2i was associated with lower risk of death in patients with and without CVD (HR: 0.56; 95% confidence interval [CI]: 0.44 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.63, respectively). There were also associations between SGLT-2i and lower risk of HF (HR: 0.72; 95% CI: 0.63 to 0.82; and HR: 0.61; 95% CI: 0.48 to 0.78, respectively) and the composite of HF or death (HR: 0.63; 95% CI: 0.57 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.62, respectively) observed in patients with and without established CVD.
Conclusions In this large, multinational, observational study, initiation of SGLT-2i was associated with lower risk of death and HF regardless of pre-existing CVD. Ongoing clinical trials will provide further evidence regarding the benefit of SGLT-2i in patients without established CVD. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614)
Supported by AstraZeneca. Dr. Cavender has received personal fees from AstraZeneca, Janssen, Merck, Sanofi-Aventis, and Chiesi; and research support from Abbott Laboratories, AstraZeneca, GlaxoSmithKline, The Medicines Company, Merck, and Takeda. Dr. Norhammar has received personal fees from AstraZeneca; and honoraria for lectures and advisory board meetings from Novo Nordisk, Boehringer Ingelheim, and Eli Lilly. Dr. Birkeland has received grants through his institution from AstraZeneca; and has received honoraria for lectures and consulting from Novo Nordisk, Sanofi, Eli Lilly, Boehringer Ingelheim, and Merck Sharp & Dohme. Dr. Jørgensen holds shares in Novo Nordisk; was recently employed by Steno Diabetes Center A/S (owned by Novo Nordisk); and has received grants from AstraZeneca. Dr. Wilding has received lecture fees from Astellas, AstraZeneca, Boehringer Ingelheim, Janssen, Eli Lilly, Novo Nordisk, Orexigen, and Sanofi; has consulted for AstraZeneca, Boehringer Ingelheim, Janssen, Eli Lilly, and Orexigen; and has received grants through his institution from Takeda, Novo Nordisk, and AstraZeneca. Dr. Bodegård is employed by AstraZeneca. Dr. Fenici is employed by AstraZeneca. Dr. Khunti is a consultant and speaker for AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Eli Lilly, Merck Sharp & Dohme, Janssen, and Boehringer Ingelheim; has received research grants from AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Eli Lilly, Boehringer Ingelheim, Merck Sharp & Dohme, and Roche; is an advisory board member for AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Eli Lilly, Merck Sharp & Dohme, Janssen, and Boehringer Ingelheim; and is supported by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care East Midlands. Dr. Fu has received grants from AstraZeneca and Merck Sharp & Dohme; and has received honoraria from Asclepius Analytics and Complete HEOR Services. Dr. Thuresson is an employee of Statisticon, for which AstraZeneca is a client. Dr. Kosiborod has received grants from AstraZeneca and Boehringer Ingelheim; is an advisory board member for AstraZeneca, Boehringer Ingelheim, Sanofi, Glytec, Novo Nordisk, Janssen, ZS Pharma, Eisai, and Merck Sharp & Dohme (Diabetes); and is a consultant for AstraZeneca, Sanofi, GlaxoSmithKline, Amgen, Janssen, Intarcia, Novo Nordisk, and ZS Pharma. Dr. Hammar is an employee of AstraZeneca. Dr. Blak is an employee of and holds shares in AstraZeneca. Dr. Wittbrodt is an employee of AstraZeneca.
- Received August 10, 2017.
- Revision received January 18, 2018.
- Accepted January 30, 2018.
- 2018 The Authors
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.